This proposal represents an expansion of our previous work, in which rhesus monkeys drink fixed amounts of methadone once daily, a regimen analogous to that used in methadone-maintenance programs for heroin abusers. At all dosage levels up to those producing physical dependence, we will investigate dose-effect relations within behavioral paradigms selected for their resemblence to important functions carried out by humans, and their proven utility in assessing the effects of experimental manipulations. First, we will quantify the speed with which these subjects can make decisions, in a paradigm which requires them to work as rapidly as they can. Second, we will analyze data from a decision-making paradigm by signal detection techniques, to determine the relative influence of drug-induced changes in discrimination ability as distinct from alterations in general responsivity. Finally, we will examine the acquisition of complex response sequences and their subsequent performance, within a paradigm which incorporates controlled variation of problem difficulty. In all these experiments, a behavioral baseline will be established pre-drug, and deviations from this will be measured continuously during the dose run-up and gradual withdrawal phases. Unlike previous experimenters, we will also continue testing for a considerable period thereafter, in order to determine whether any effects persist post-methadone. BIBLIOGRAPHIC REFERENCES: Eibergen, R. D. & Carlson, K. R. Behavioral evidence for dopaminergic supersensitivity following chronic treatment with methadone or chlorpromazine in the guinea pig. Pharmacology 48: 139-146, 1976(a). Eibergen, R. D. and Carlson, K. R. Dyskinesias in monkeys: Interaction of methamphetamine with prior methadone treatment. Pharmac. Biochem. Behav. 5: 175-187, 1976(b).